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The Legionella collagen-like protein employs a unique binding mechanism for the recognition of host glycosaminoglycans.

ABSTRACT: Bacterial adhesion is a fundamental process which enables colonisation of niche environments and is key for infection. However, in Legionella pneumophila, the causative agent of Legionnaires' disease, these processes are not well understood. The Legionella collagen-like protein (Lcl) is an extracellular peripheral membrane protein that recognises sulphated glycosaminoglycans (GAGs) on the surface of eukaryotic cells, but also stimulates bacterial aggregation in response to divalent cations. Here we report the crystal structure of the Lcl C-terminal domain (Lcl-CTD) and present a model for intact Lcl. Our data reveal that Lcl-CTD forms an unusual dynamic trimer arrangement with a positively charged external surface and a negatively charged solvent exposed internal cavity. Through Molecular Dynamics (MD) simulations, we show how the GAG chondroitin-4-sulphate associates with the Lcl-CTD surface via unique binding modes. Our findings show that Lcl homologs are present across both the Pseudomonadota and Fibrobacterota-Chlorobiota-Bacteroidota phyla and suggest that Lcl may represent a versatile carbohydrate binding mechanism.

SUBMITTER: Rehman S

PROVIDER: S-EPMC10723406 | biostudies-literature | 2023 Dec

REPOSITORIES: biostudies-literature

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The Legionella collagen-like protein employs a unique binding mechanism for the recognition of host glycosaminoglycans.

Rehman Saima S Antonovic Anna K AK McIntire Ian E IE Zheng Huaixin H Cleaver Leanne L Adams Carlton O CO Portlock Theo T Richardson Katherine K Shaw Rosie R Oregioni Alain A Mastroianni Giulia G Whittaker Sara B-M SB Kelly Geoff G Fornili Arianna A Cianciotto Nicholas P NP Garnett James A JA

bioRxiv : the preprint server for biology 20231210

Bacterial adhesion is a fundamental process which enables colonisation of niche environments and is key for infection. However, in Legionella pneumophila, the causative agent of Legionnaires' disease, these processes are not well understood. The Legionella collagen-like protein (Lcl) is an extracellular peripheral membrane protein that recognises sulphated glycosaminoglycans (GAGs) on the surface of eukaryotic cells, but also stimulates bacterial aggregation in response to divalent ...[more]

PMID: 38106198

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Project description:Interleukin 18 (IL18) is a cytokine that plays an important role in inflammation as well as host defense against microbes. Mammals encode a soluble inhibitor of IL18 termed IL18 binding protein (IL18BP) that modulates IL18 activity through a negative feedback mechanism. Many poxviruses encode homologous IL18BPs, which contribute to virulence. Previous structural and functional studies on IL18 and IL18BPs revealed an essential binding hot spot involving a lysine on IL18 and two aromatic residues on IL18BPs. The aromatic residues are conserved among the very diverse mammalian and poxviruses IL18BPs with the notable exception of yatapoxvirus IL18BPs, which lack a critical phenylalanine residue. To understand the mechanism by which yatapoxvirus IL18BPs neutralize IL18, we solved the crystal structure of the Yaba-Like Disease Virus (YLDV) IL18BP and IL18 complex at 1.75 Å resolution. YLDV-IL18BP forms a disulfide bonded homo-dimer engaging IL18 in a 2∶2 stoichiometry, in contrast to the 1∶1 complex of ectromelia virus (ECTV) IL18BP and IL18. Disruption of the dimer interface resulted in a functional monomer, however with a 3-fold decrease in binding affinity. The overall architecture of the YLDV-IL18BP:IL18 complex is similar to that observed in the ECTV-IL18BP:IL18 complex, despite lacking the critical lysine-phenylalanine interaction. Through structural and mutagenesis studies, contact residues that are unique to the YLDV-IL18BP:IL18 binding interface were identified, including Q67, P116 of YLDV-IL18BP and Y1, S105 and D110 of IL18. Overall, our studies show that YLDV-IL18BP is unique among the diverse family of mammalian and poxvirus IL-18BPs in that it uses a bivalent binding mode and a unique set of interacting residues for binding IL18. However, despite this extensive divergence, YLDV-IL18BP binds to the same surface of IL18 used by other IL18BPs, suggesting that all IL18BPs use a conserved inhibitory mechanism by blocking a putative receptor-binding site on IL18.

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The Legionella collagen-like protein employs a unique binding mechanism for the recognition of host glycosaminoglycans.

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The <i>Legionella</i> collagen-like protein employs a unique binding mechanism for the recognition of host glycosaminoglycans.

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The Legionella collagen-like protein employs a unique binding mechanism for the recognition of host glycosaminoglycans.

Publications

The &lt;i&gt;Legionella&lt;/i&gt; collagen-like protein employs a unique binding mechanism for the recognition of host glycosaminoglycans.

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OmicsDI is part of the ELIXIR infrastructure

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The <i>Legionella</i> collagen-like protein employs a unique binding mechanism for the recognition of host glycosaminoglycans.